This proposal describes a new technology called "preparative in situ hybridization (Prep-I.S.H.), which is capable of isolating a set of cDNA or genomic clones according to their chromosome location. The technology takes advantage of in situ hybridization of cloned DNAs to metaphase chromosome spreads, chromosome microdissection, and the polymerase chain reaction (PCR). We propose to use this technology to develop a set of chromosome-specific painting probes for the mouse. The demonstration case, a chromosome 11-specific probe, will be used to paint the mitotic chromosome 11s derived from the mouse lymphoma assay (MLA).